Primary hyperparathyroidism affects 0.2% to 0.5% of the population, with approximately 100,000 new cases in the U.S. each year. Women are three times more commonly affected than men and the incidence increases with age, so that up to 2% of post-menopausal women are estimated to have this disease. Associated morbidity and sequelae include decreased bone mineral density, fractures, and kidney stones. Currently, little is known about risk factors for developing primary hyperparathyroidism. We propose to study prospectively the relations between dietary, hormonal, and lifestyle risk factors and the development of primary hyperparathyroidism in two large, ongoing cohort studies of women: the Nurses Health Studies I (N=85,061) and II (N=75,815). The parathyroid adenomas of sporadic primary hyperparathyroidism are monoclonal, suggesting that these neoplasms originate from single cells with a growth conferring mutation. Factors that cause parathyroid hyperplasia therefore may increase the risk for developing primary hyperparathyroidism. The specific aims are the following: Aim 1) Diet. We hypothesize that lower calcium intake, higher phosphorous intake, and lower magnesium intake are independently associated with higher risk of developing primary hyperparathyroidism. Aim 2) Menopausal Status and Post-Menopausal Hormone Use. The incidence of primary hyperparathyroidism rises sharply after menopause. We hypothesize that menopause is independently associated with a higher risk of developing primary hyperparathyroidism and that post-menopausal hormone use is associated with a lower risk of developing primary hyperparathyroidism. Aim 3) Lifestyle Factors. We hypothesize that higher body mass index, lower estimated 25- hydroxyvitamin D levels, and higher alcohol consumption are associated with the risk of developing primary hyperparathyroidism. The outcome of our prospective cohort studies will be the incidence of primary hyperparathyroidism, with all cases confirmed by medical review. Because we expect to have over 1200 cases, the statistical power will be high. For example, the power to detect a hazard ratio of 1.4 across quintiles of calcium is 0.98. This study represents the first large-scale prospective effort to identify modifiable risk factors for primary hyperparathyroidism. Findings from this study could have important public health implications by preventing disease development and its associated sequelae. Finally, the creation of this large cohort of primary hyperparathyroidism cases will serve as a valuable resource for future research.